Nucleic acids are the fundamental informational molecules of all living organisms. We propose to explore the three-dimensional structural details of the interactions of nucleic acids with themselves and other biologically important molecules by means of single crystal x-ray crystallography. We wish to explore the non-covalent sequence specific recognition of nucleic acids by drugs, peptides, cations, as well as water and other appropriate probes. The primary path by which these phenomena will be studied will be by crystallization of short, defined sequence fragments of double helical nucleic acids complexed both with cations and drugs which bind them in a sequence specific fashion. We believe that these studies will provide much hard geometric data about the intimate conformational and configurational details of the sequence specific recognition of nucleic acids, a phenomenon which we are also modelling on the computer. Via this data, we hope to gain insight into the molecular basis of the mode of drug action and the mechanism of gene expression.